Functional Toll-like receptors in primary first trimester trophoblasts

Tangerås, Line Haugstad; Stødle, Guro; Olsen, Gunn-Hege; Leknes, Ann-Helen; Gundersen, Astrid; Skei, Bente; Vikdal, Anne Jorunn; Ryan, Liv; Steinkjer, Bjørg; Myklebost, Merete F.; Langaas, Mette; Austgulen, Rigmor; Iversen, Ann‐Charlotte

doi:10.1016/j.placenta.2013.06.099

Cited by 11 publications

(22 citation statements)

References 36 publications

(61 reference statements)

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“…TLR3 gene expression was found in all cell lines except JAR, and TLR5 was detected in all cell lines except SGHPL-5. BeWo expressed nine of the ten TLR mRNAs and mostly resembled the TLR gene expression profile of primary first trimester trophoblasts ( Table 2, [7]). …”

Section: Tlr Gene Expression In Seven Trophoblast Cell Linesmentioning

confidence: 90%

“…Ten different human TLRs, each responding to a specific set of ligands, have been identified [4]. TLR expression and activation in primary trophoblasts [5][6][7][8][9][10] may contribute substantially to development of inflammatory pregnancy complications such as preeclampsia [11][12][13]. In Tangerås/Stødle et al [7] we demonstrated a broad functional TLR profile in primary first trimester trophoblasts, while the trophoblast cell line BeWo showed no TLR mediated cytokine response.…”

Section: Introductionmentioning

confidence: 91%

“…TLR1-10 gene expression was analyzed by RT-qPCR as previously described [7]. In short, 1.5 μl cDNA (iScript/qScript cDNA synthesis kit, Bio-Rad, Hercules, CA/Quanta, Gaithersburg, Maryland) was added to SYBR Green Supermix/FastMix (Bio-Rad/Quanta) together with 400 nM/300 nM of forward and reverse primers for TLR1-10 or the reference gene TATA box binding protein (TBP) (BioRad/Quanta) [7].…”

Section: Tlr Gene Expressionmentioning

confidence: 99%

“…In short, 1.5 μl cDNA (iScript/qScript cDNA synthesis kit, Bio-Rad, Hercules, CA/Quanta, Gaithersburg, Maryland) was added to SYBR Green Supermix/FastMix (Bio-Rad/Quanta) together with 400 nM/300 nM of forward and reverse primers for TLR1-10 or the reference gene TATA box binding protein (TBP) (BioRad/Quanta) [7]. The samples were analyzed in triplicates on a Chromo4 detector using MJ Opticon Monitor software version 3.1 (Bio-Rad) at 95 °C for 5 min, 40 cycles of 95 °C for 5 s, 60 °C to 66 °C for 10 s, and 72 °C for 8 s.…”

Section: Tlr Gene Expressionmentioning

confidence: 99%

“…For comparison, data on TLR1-10 gene expression and activation in primary first trimester trophoblasts from our previous publication [7] was included. Trophoblasts were isolated from placental tissue collected from six healthy women undergoing surgically-induced elective abortions at 6-12 weeks gestation.…”

Section: Primary First Trimester Trophoblastsmentioning

confidence: 99%

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Toll-like receptor profiling of seven trophoblast cell lines warrants caution for translation to primary trophoblasts

et al. 2015

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Section: Tlr Gene Expression In Seven Trophoblast Cell Linesmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 91%

Section: Tlr Gene Expressionmentioning

confidence: 99%

Section: Tlr Gene Expressionmentioning

confidence: 99%

Section: Primary First Trimester Trophoblastsmentioning

confidence: 99%

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Toll-like receptor profiling of seven trophoblast cell lines warrants caution for translation to primary trophoblasts

et al. 2015

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Human endogenous retrovirus envelope proteins target dendritic cells to suppress T‐cell activation

et al. 2015

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Though mostly defective, human endogenous retroviruses (HERV)can retain open reading frames, which are especially expressed in the placenta. There, the envelope (env) proteins of HERV-W (Syncytin-1), HERV-FRD (Syncytin-2), and HERV-K (HML-2) were implicated in tolerance against the semi-allogenic fetus. Here, we show that the known HERV envbinding receptors ASCT-1 and -2 and MFSD2 are expressed by DCs and T-cells. When used as effectors in coculture systems, CHO cells transfected to express Syncytin-1, -2, or HML-2 did not affect T-cell expansion or overall LPS-driven phenotypic DC maturation, however, promoted release of IL-12 and TNF-α rather than IL-10. In contrast, HERV env expressing choriocarcinoma cell lines suppressed T-cell proliferation and LPS-induced TNF-α and IL-12 release, however, promoted IL-10 accumulation, indicating that these effects might not rely on HERV env interactions. However, DCs conditioned by choriocarcinoma, but also transgenic CHO cells failed to promote allogenic T-cell expansion. This was associated with a loss of DC/T-cell conjugate frequencies, impaired Ca 2+ mobilization, and aberrant patterning of f-actin and tyrosine phosphorylated proteins in T-cells. Altogether, these findings suggest that HERV env proteins target T-cell activation indirectly by modulating the stimulatory activity of DCs.Keywords: DCs r DC/T-cell conjugates r HERV r Immune tolerance r Immunological synapse r T-cell activation Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionHuman endogenous retroviruses (HERVs) are estimated to comprise about 8% of the human genome [1]. They are mainly germline transmitted. HERVs are typically defective as a result of multiple mutations in their genomes, and it is therefore only on exception that viral particles can be produced [1,2]. Endogenous retroviruses (ERVs) can substantially regulate host cell gene expression and functions. In addition to viral transcripts, ERV encoded proteins translated from intact ORFs were implicated Correspondence: Dr. Sibylle Schneider-Schaulies e-mail: s-s-s@vim.uni-wuerzburg.de in both pathological and physiological processes [3]. The latter has for instance been revealed for the envelope (env) regions of three HERVs (ERV-3, HERV-W, and HERV-FRD). These are highly expressed in early and late placentae, and their importance in successful accomplishment of pregnancy has been suggested [4][5][6][7][8][9][10], not least because spontaneous abortions or complications of gestation like preeclampsia are associated with reduced levels of HERV env proteins [11,12]. In fact, their expression has been found crucial in the intrauterine fetal development in promoting syncytiotrophoblast formation, while the HERV-FRD env was also associated with fetomaternal tolerance to prevent rejection of the fetus [13][14][15][16][17].Immunodeficiency is commonly associated with retroviral infections (for a recent review see [18] effector mechanisms studied, immunosuppressive domains (ISD) we...

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Upregulation of Toll‐like receptor 4 through anti‐miR‐Let‐7a enhances blastocyst attachment to endometrial cells in mice

Hosseini

Salehi

2020

Journal Cellular Physiology

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Despite encouraging advances in fertility technology, the success rate of an ongoing pregnancy is relatively low and predominantly associated with implantation failure. Inflammatory responses are beneficial in the fetomaternal interface and supposedly accelerate the chances for successful implantation. The current study aims to determine the effect of Toll‐like receptor 4 (TLR4) overexpression in mouse blastocysts via Let‐7a downregulation using intracytoplasmic sperm injection‐sperm‐mediated gene transfer on embryo attachment rate. The pLenti‐III‐GFP‐miR‐Off‐Let‐7a vector was transmitted to oocytes derived via in vitro maturation (IVM) and in vivo oocytes by using NaOH‐treated spermatozoa. Let‐7a and TLR4 expression levels were evaluated by quantitative real‐time polymerase chain reaction (qRT‐PCR), immunocytochemistry, and western blot analysis in both oocytes and embryos. Blastocyst adhesion on the endometrial cells was monitored by microscopic analysis. qRT‐PCR results showed that Let‐7a expression decreased in the IVM (GV‐MII) oocytes compared to the in vivo oocyte (MII) group (p < .05). TLR4 showed a higher expression in GV‐MII oocytes at both the gene and protein levels (p < .05). Following anti‐miR‐Let‐7a transmission, the TLR4 expression level was significantly upregulated in embryos compared with the control groups (p < .05). Attachment and migration of trophoblasts cells towards endometrial cells dramatically increased compared to the control group (p < .05). Based on our results, we concluded that Let‐7a might mediate embryo attachment through regulation of TLR4 expression levels.

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Functional Toll-like receptors in primary first trimester trophoblasts

Cited by 11 publications

References 36 publications

Toll-like receptor profiling of seven trophoblast cell lines warrants caution for translation to primary trophoblasts

Toll-like receptor profiling of seven trophoblast cell lines warrants caution for translation to primary trophoblasts

Human endogenous retrovirus envelope proteins target dendritic cells to suppress T‐cell activation

Upregulation of Toll‐like receptor 4 through anti‐miR‐Let‐7a enhances blastocyst attachment to endometrial cells in mice

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